Abstract 1704: Linking mitochondrial epigenetics to tumorigenesis and the cancer theory of Warburg.

Abstract Otto Warburg first proposed that respiratory insufficiency was the common metabolic hallmark of all tumor cells. Respiratory insufficiency is the precursor to aerobic fermentation (Warburg effect), and can also be linked to dysregulated proliferation and to the genomic abnormalities seen in the majority of cancers. It is well documented that tumorigenicity can be suppressed in a broad range of tumor types when cytoplasm from enucleated normal cells, containing normal mitochondria, is fused with nucleated tumor cells to form cybrids. Tumorigenicity is also suppressed in a broad range of tumors following transplantation of the nucleus from tumor cells into enucleated eggs or somatic cells, indicating that tumor nuclei are capable of directing development despite the persistence of tumor-associated mutations. Tumor cell mutations seem to abort development, rather than induce tumorigenesis. In contrast to the tumor suppressive effects of cytoplasm containing normal mitochondria, either cell death or tumor cells arise when nuclei from non-tumorigenic normal cells are fused with cytoplasm from tumor cells. The results from these studies indicate that nuclear genomic defects alone cannot produce tumors, and that normal mitochondria can suppress tumorigenesis. The findings, when viewed collectively, support Warburg's central theory and suggest that mitochondrial epigenetics drives tumorigenesis. Supported in part from the Boston College Res. Expense Fund. Citation Format: Thomas N. Seyfried. Linking mitochondrial epigenetics to tumorigenesis and the cancer theory of Warburg. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1704. doi:10.1158/1538-7445.AM2013-1704